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2Endocrine System: OverviewEndocrine system – the body’s second great controlling system which influences metabolic activities of cells by means of hormonesEndocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymusThe pancreas and gonads produce both hormones and exocrine productsChapter 16: Endocrine System

3Endocrine System: OverviewThe hypothalamus has both neural functions and releases hormonesOther tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heartChapter 16: Endocrine System

5Autocrines and ParacrinesAutocrines – chemicals that exert their effects on the same cells that secrete themParacrines – locally acting chemicals that affect cells other than those that secrete themThese are not considered hormones since hormones are long-distance chemical signalsChapter 16: Endocrine System

6Chapter 16: Endocrine SystemHormonesHormones – chemical substances secreted by cells into the extracellular fluidsRegulate the metabolic function of other cellsHave lag times ranging from seconds to hoursTend to have prolonged effectsAre classified as amino acid-based hormones, or steroidsEicosanoids – biologically active lipids with local hormone–like activityChapter 16: Endocrine System

9Mechanism of Hormone ActionHormones produce one or more of the following cellular changes in target cellsAlter plasma membrane permeabilityStimulate protein synthesisActivate or deactivate enzyme systemsInduce secretory activityStimulate mitosisChapter 16: Endocrine System

16Target Cell SpecificityHormones circulate to all tissues but only activate cells referred to as target cellsTarget cells must have specific receptors to which the hormone bindsThese receptors may be intracellular or located on the plasma membraneChapter 16: Endocrine System

17Target Cell SpecificityExamples of hormone activityACTH receptors are only found on certain cells of the adrenal cortexThyroxin receptors are found on nearly all cells of the bodyChapter 16: Endocrine System

18Target Cell ActivationTarget cell activation depends on three factorsBlood levels of the hormoneRelative number of receptors on the target cellThe affinity of those receptors for the hormoneUp-regulation – target cells form more receptors in response to the hormoneDown-regulation – target cells lose receptors in response to the hormoneChapter 16: Endocrine System

19Hormone Concentrations in the BloodHormones circulate in the blood in two forms – free or boundSteroids and thyroid hormone are attached to plasma proteinsAll others are unencumberedChapter 16: Endocrine System

20Hormone Concentrations in the BloodConcentrations of circulating hormone reflect:Rate of releaseSpeed of inactivation and removal from the bodyHormones are removed from the blood by:Degrading enzymesThe kidneysLiver enzyme systemsChapter 16: Endocrine System

21Interaction of Hormones at Target CellsThree types of hormone interactionPermissiveness – one hormone cannot exert its effects without another hormone being presentSynergism – more than one hormone produces the same effects on a target cellAntagonism – one or more hormones opposes the action of another hormoneChapter 16: Endocrine System

22Control of Hormone ReleaseBlood levels of hormones:Are controlled by negative feedback systemsVary only within a narrow desirable rangeHormones are synthesized and released in response to:Humoral stimuliNeural stimuliHormonal stimuliChapter 16: Endocrine System

28Nervous System ModulationThe nervous system modifies the stimulation of endocrine glands and their negative feedback mechanismsThe nervous system can override normal endocrine controlsFor example, control of blood glucose levelsNormally the endocrine system maintains blood glucoseUnder stress, the body needs more glucoseThe hypothalamus and the sympathetic nervous system are activated to supply ample glucoseChapter 16: Endocrine System

29Major Endocrine Organs: Pituitary (Hypophysis)Pituitary gland – two-lobed organ that secretes nine major hormonesNeurohypophysis – posterior lobe (neural tissue) and the infundibulumReceives, stores, and releases hormones from the hypothalamusAdenohypophysis – anterior lobe, made up of glandular tissueSynthesizes and secretes a number of hormonesChapter 16: Endocrine System

31Pituitary-Hypothalamic Relationships: Posterior LobeThe posterior lobe is a downgrowth of hypothalamic neural tissueHas a neural connection with the hypothalamus (hypothalamic-hypophyseal tract)Nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH)These hormones are transported to the posterior pituitaryChapter 16: Endocrine System

32Pituitary-Hypothalamic Relationships: Anterior LobeThe anterior lobe of the pituitary is an outpocketing of the oral mucosaThere is no direct neural contact with the hypothalamusChapter 16: Endocrine System

35Adenophypophyseal HormonesThe six hormones of the adenohypophysis:Are abbreviated as GH, TSH, ACTH, FSH, LH, and PRLRegulate the activity of other endocrine glandsIn addition, pro-opiomelanocortin (POMC):Has been isolated from the pituitaryIs enzymatically split into ACTH, opiates, and MSHChapter 16: Endocrine System

36Activity of the AdenophypophysisThe hypothalamus sends a chemical stimulus to the anterior pituitaryReleasing hormones stimulate the synthesis and release of hormonesInhibiting hormones shut off the synthesis and release of hormonesChapter 16: Endocrine System

38Chapter 16: Endocrine SystemGrowth Hormone (GH)Produced by somatotropic cells of the anterior lobe that:Stimulate most cells, but target bone and skeletal musclePromote protein synthesis and encourage the use of fats for fuelMost effects are mediated indirectly by somatomedinsChapter 16: Endocrine System

42Thyroid Stimulating Hormone (Thyrotropin)Tropic hormone that stimulates the normal development and secretory activity of the thyroid glandTriggered by hypothalamic peptide thyrotropin-releasing hormone (TRH)Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSHChapter 16: Endocrine System

43Adrenocorticotropic Hormone (Corticotropin)Stimulates the adrenal cortex to release corticosteroidsTriggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythmInternal and external factors such as fever, hypoglycemia, and stressors can trigger the release of CRHChapter 16: Endocrine System

44Chapter 16: Endocrine SystemGonadotropinsGonadotropins – follicle-stimulating hormone (FSH) and luteinizing hormone (LH)Regulate the function of the ovaries and testesFSH stimulates gamete (egg or sperm) productionAbsent from the blood in prepubertal boys and girlsTriggered by the hypothalamic gonadotropin-releasing hormone (GnRH) during and after pubertyChapter 16: Endocrine System

45Functions of GonadotropinsIn femalesLH works with FSH to cause maturation of the ovarian follicleLH works alone to trigger ovulation (expulsion of the egg from the follicle)LH promotes synthesis and release of estrogens and progesteroneChapter 16: Endocrine System

46Functions of GonadotropinsIn malesLH stimulates interstitial cells of the testes to produce testosteroneLH is also referred to as interstitial cell-stimulating hormone (ICSH)Chapter 16: Endocrine System

47Chapter 16: Endocrine SystemProlactin (PRL)In females, stimulates milk production by the breastsTriggered by the hypothalamic prolactin-releasing hormone (PRH)Inhibited by prolactin-inhibiting hormone (PIH)Blood levels rise toward the end of pregnancySuckling stimulates PRH release and encourages continued milk productionChapter 16: Endocrine System

48The Posterior Pituitary and Hypothalamic HormonesPosterior pituitary – made of axons of hypothalamic neurons, stores antidiuretic hormone (ADH) and oxytocinADH and oxytocin are synthesized in the hypothalamusADH influences water balanceOxytocin stimulates smooth muscle contraction in breasts and uterusBoth use PIP-calcium second-messenger mechanismChapter 16: Endocrine System

49Chapter 16: Endocrine SystemOxytocinOxytocin is a strong stimulant of uterine contractionRegulated by a positive feedback mechanism to oxytocin in the bloodThis leads to increased intensity of uterine contractions, ending in birthOxytocin triggers milk ejection (“letdown” reflex) in women producing milkChapter 16: Endocrine System

50Chapter 16: Endocrine SystemOxytocinSynthetic and natural oxytocic drugs are used to induce or hasten laborPlays a role in sexual arousal and satisfaction in males and nonlactating femalesChapter 16: Endocrine System

51Antidiuretic Hormone (ADH)ADH helps to avoid dehydration or water overloadPrevents urine formationOsmoreceptors monitor the solute concentration of the bloodWith high solutes, ADH is synthesized and released, thus preserving waterWith low solutes, ADH is not released, thus causing water loss from the bodyAlcohol inhibits ADH release and causes copious urine outputChapter 16: Endocrine System

52Chapter 16: Endocrine SystemThyroid GlandThe largest endocrine gland, located in the anterior neck, consists of two lateral lobes connected by a median tissue mass called the isthmusComposed of follicles that produce the glycoprotein thyroglobulinColloid (thyroglobulin + iodine) fills the lumen of the follicles and is the precursor of thyroid hormoneOther endocrine cells, the parafollicular cells, produce the hormone calcitoninChapter 16: Endocrine System

56Synthesis of Thyroid HormoneThyroglobulin is synthesized and discharged into the lumenIodides (I–) are actively taken into the cell, oxidized to iodine (I2), and released into the lumenIodine attaches to tyrosine, mediated by peroxidase enzymes, forming T1 (monoiodotyrosine, or MIT), and T2 (diiodotyrosine, or DIT)Iodinated tyrosines link together to form T3 and T4Colloid is then endocytosed and combined with a lysosome, where T3 and T4 are cleaved and diffuse into the bloodstreamChapter 16: Endocrine System

58Transport and Regulation of THT4 and T3 bind to thyroxine-binding globulins (TBGs) produced by the liverBoth bind to target receptors, but T3 is ten times more active than T4Peripheral tissues convert T4 to T3Mechanisms of activity are similar to steroidsRegulation is by negative feedbackHypothalamic thyrotropin-releasing hormone (TRH) can overcome the negative feedbackChapter 16: Endocrine System

63Effects of Parathyroid HormonePTH release increases Ca2+ in the blood as it:Stimulates osteoclasts to digest bone matrixEnhances the reabsorption of Ca2+ and the secretion of phosphate by the kidneysIncreases absorption of Ca2+ by intestinal mucosal cellsRising Ca2+ in the blood inhibits PTH releaseChapter 16: Endocrine System

68Chapter 16: Endocrine SystemMineralocorticoidsRegulate the electrolyte concentrations of extracellular fluidsAldosterone – most important mineralocorticoidMaintains Na+ balance by reducing excretion of sodium from the bodyStimulates reabsorption of Na+ by the kidneysChapter 16: Endocrine System

74Gonadocorticoids (Sex Hormones)Most gonadocorticoids secreted are androgens (male sex hormones), and the most important one is testosteroneAndrogens contribute to:The onset of pubertyThe appearance of secondary sex characteristicsSex drive in femalesAndrogens can be converted into estrogens after menopauseChapter 16: Endocrine System

75Chapter 16: Endocrine SystemAdrenal MedullaMade up of chromaffin cells that secrete epinephrine and norepinephrineSecretion of these hormones causes:Blood glucose levels to riseBlood vessels to constrictThe heart to beat fasterBlood to be diverted to the brain, heart, and skeletal muscleChapter 16: Endocrine System

76Chapter 16: Endocrine SystemAdrenal MedullaEpinephrine is the more potent stimulator of the heart and metabolic activitiesNorepinephrine is more influential on peripheral vasoconstriction and blood pressureChapter 16: Endocrine System

79Chapter 16: Endocrine SystemGlucagonA 29-amino-acid polypeptide hormone that is a potent hyperglycemic agentIts major target is the liver, where it promotes:Glycogenolysis – the breakdown of glycogen to glucoseGluconeogenesis – synthesis of glucose from lactic acid and noncarbohydratesRelease of glucose to the blood from liver cellsChapter 16: Endocrine System

85Chapter 16: Endocrine SystemGonads: FemalePaired ovaries in the abdominopelvic cavity produce estrogens and progesteroneThey are responsible for:Maturation of the reproductive organsAppearance of secondary sexual characteristicsBreast development and cyclic changes in the uterine mucosaChapter 16: Endocrine System

87Chapter 16: Endocrine SystemPineal GlandSmall gland hanging from the roof of the third ventricle of the brainSecretory product is melatoninMelatonin is involved with:Day/night cyclesPhysiological processes that show rhythmic variations (body temperature, sleep, appetite)Chapter 16: Endocrine System

88Chapter 16: Endocrine SystemThymusLobulated gland located deep to the sternum in the thoraxMajor hormonal products are thymopoietins and thymosinsThese hormones are essential for the development of the T lymphocytes (T cells) of the immune systemChapter 16: Endocrine System

90Other Hormone-Producing StructuresKidneys – secrete erythropoietin, which signals the production of red blood cellsSkin – produces cholecalciferol, the precursor of vitamin DAdipose tissue – releases leptin, which is involved in the sensation of satiety, and stimulates increased energy expenditureChapter 16: Endocrine System

91Developmental AspectsHormone-producing glands arise from all three germ layersEndocrine glands derived from mesoderm produce steroid hormonesEndocrine organs operate smoothly throughout lifeMost endocrine glands show structural changes with age, but hormone production may or may not be affectedChapter 16: Endocrine System

92Developmental AspectsExposure to pesticides, industrial chemicals, arsenic, dioxin, and soil and water pollutants disrupts hormone functionSex hormones, thyroid hormone, and glucocorticoids are vulnerable to the effects of pollutantsInterference with glucocorticoids may help explain high cancer rates in certain areasChapter 16: Endocrine System

93Developmental AspectsOvaries undergo significant changes with age and become unresponsive to gonadotropinsFemale hormone production declines, the ability to bear children ends, and problems associated with estrogen deficiency (e.g., osteoporosis) begin to occurTestosterone also diminishes with age, but effect is not usually seen until very old ageChapter 16: Endocrine System

94Developmental AspectsGH levels decline with age and this accounts for muscle atrophy with ageSupplemental GH may spur muscle growth, reduce body fat, and help physiqueTH declines with age, causing lower basal metabolic ratesPTH levels remain fairly constant with age, and lack of estrogen in women makes them more vulnerable to bone-demineralizing effects of PTHChapter 16: Endocrine System